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1.
Front Immunol ; 13: 890836, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35747143

RESUMO

Background: Colorectal cancer (CRC) is a heterogeneous disease with variable mutational profile and tumour microenvironment composition that influence tumour progression and response to treatment. While chemoresistant and poorly immunogenic CRC remains a challenge, the development of new strategies guided by biomarkers could help stratify and treat patients. Allogeneic NK cell transfer emerges as an alternative against chemoresistant and poorly immunogenic CRC. Methods: NK cell-related immunological markers were analysed by transcriptomics and immunohistochemistry in human CRC samples and correlated with tumour progression and overall survival. The anti-tumour ability of expanded allogeneic NK cells using a protocol combining cytokines and feeder cells was analysed in vitro and in vivo and correlated with CRC mutational status and the expression of ligands for immune checkpoint (IC) receptors regulating NK cell activity. Results: HLA-I downmodulation and NK cell infiltration correlated with better overall survival in patients with a low-stage (II) microsatellite instability-high (MSI-H) CRC, suggesting a role of HLA-I as a prognosis biomarker and a potential benefit of NK cell immunotherapy. Activated allogeneic NK cells were able to eliminate CRC cultures without PD-1 and TIM-3 restriction but were affected by HLA-I expression. In vivo experiments confirmed the efficacy of the therapy against both HLA+ and HLA- CRC cell lines. Concomitant administration of pembrolizumab failed to improve tumour control. Conclusions: Our results reveal an immunological profile of CRC tumours in which immunogenicity (MSI-H) and immune evasion mechanisms (HLA downmodulation) favour NK cell immunosurveillance at early disease stages. Accordingly, we have shown that allogeneic NK cell therapy can target tumours expressing mutations conferring poor prognosis regardless of the expression of T cell-related inhibitory IC ligands. Overall, this study provides a rationale for a new potential basis for CRC stratification and NK cell-based therapy.


Assuntos
Neoplasias Colorretais , Instabilidade de Microssatélites , Neoplasias Colorretais/patologia , Humanos , Imunoterapia/métodos , Células Matadoras Naturais , Ligantes , Microambiente Tumoral
2.
Sensors (Basel) ; 22(11)2022 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-35684649

RESUMO

The recognition of Activities of Daily Living (ADL) has been a widely debated topic, with applications in a vast range of fields. ADL recognition can be accomplished by processing data from wearable sensors, specially located at the lower trunk, which appears to be a suitable option in uncontrolled environments. Several authors have addressed ADL recognition using Artificial Intelligence (AI)-based algorithms, obtaining encouraging results. However, the number of ADL recognized by these algorithms is still limited, rarely focusing on transitional activities, and without addressing falls. Furthermore, the small amount of data used and the lack of information regarding validation processes are other drawbacks found in the literature. To overcome these drawbacks, a total of nine public and private datasets were merged in order to gather a large amount of data to improve the robustness of several ADL recognition algorithms. Furthermore, an AI-based framework was developed in this manuscript to perform a comparative analysis of several ADL Machine Learning (ML)-based classifiers. Feature selection algorithms were used to extract only the relevant features from the dataset's lower trunk inertial data. For the recognition of 20 different ADL and falls, results have shown that the best performance was obtained with the K-NN classifier with the first 85 features ranked by Relief-F (98.22% accuracy). However, Ensemble Learning classifier with the first 65 features ranked by Principal Component Analysis (PCA) presented 96.53% overall accuracy while maintaining a lower classification time per window (0.039 ms), showing a higher potential for its usage in real-time scenarios in the future. Deep Learning algorithms were also tested. Despite its outcomes not being as good as in the prior procedure, their potential was also demonstrated (overall accuracy of 92.55% for Bidirectional Long Short-Term Memory (LSTM) Neural Network), indicating that they could be a valid option in the future.


Assuntos
Atividades Cotidianas , Inteligência Artificial , Acidentes por Quedas/prevenção & controle , Algoritmos , Humanos , Redes Neurais de Computação
3.
Molecules ; 27(10)2022 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-35630668

RESUMO

Fibroblast growth factor 21 (FGF21) signaling and genetic factors are involved in non-alcoholic fatty liver disease (NAFLD) pathogenesis. However, these factors have rarely been studied in type 2 diabetes mellitus (T2D) patients from admixed populations such as in those of Brazil. Therefore, we aimed to evaluate rs738409 patanin-like phospholipase domain-containing protein (PNPLA3) and rs499765 FGF21 polymorphisms in T2D, and their association with NAFLD, liver fibrosis, and serum biomarkers (FGF21 and cytokeratin 18 levels). A total of 158 patients were included, and the frequency of NAFLD was 88.6%, which was independently associated with elevated body mass index. Significant liver fibrosis (≥F2) was detected by transient elastography (TE) in 26.8% of NAFLD patients, and was independently associated with obesity, low density lipoprotein, and gamma-glutamyl transferase (GGT). PNPLA3 GG genotype and GGT were independently associated with cirrhosis. PNPLA3 GG genotype patients had higher GGT and AST levels; PNPLA3 GG carriers had higher TE values than CG patients, and FGF21 CG genotype patients showed lower gamma-GT values than CC patients. No differences were found in serum values of FGF21 and CK18 in relation to the presence of NAFLD or liver fibrosis. The proportion of NAFLD patients with liver fibrosis was relevant in the present admixed T2D population, and was associated with PNPLA3 polymorphisms.


Assuntos
Aciltransferases/sangue , Diabetes Mellitus Tipo 2 , Fatores de Crescimento de Fibroblastos/sangue , Hepatopatia Gordurosa não Alcoólica , Fosfolipases A2 Independentes de Cálcio/sangue , Biomarcadores , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/genética , Humanos , Lipase/genética , Lipase/metabolismo , Cirrose Hepática/complicações , Cirrose Hepática/genética , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/genética
4.
PLoS One ; 17(5): e0268254, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35580110

RESUMO

INTRODUCTION: The Handheld Dynamometer (HHD) has the potential to overcome some of the logistic and economic limitations of isokinetic dynamometers for measuring knee extension muscle strength. However, its reliability has not been fully assessed. The purpose of this study is to measure intra and inter-rater reliability of HHD for knee extension strength in patients receiving rehabilitation treatment, as well as to understand in which conditions is the reliability higher. METHODS: Twenty-nine patients admitted in an inpatient Physical Medicine and Rehabilitation unit were consecutively included in this cross-sectional study. Two experienced and two inexperienced physicians made two assessments of knee extension strength with HHD, separated by three hours. Intraclass Correlation Coefficients (ICC), absolute differences between assessments, and correlations between strength and functional variables were calculated. RESULTS: Intra and inter-rater ICC were overall high (≥ 0.950 and 0.927, respectively). Higher values were found when average of two measurements were made for estimating intra-rater ICC (ICC = 0.978; 95%CI = 0.969-0.985) but not for inter-rater ICC. ICC were not statistically significantly different when calculated based on measurements performed by inexperienced physicians and experienced ones. There was a moderate correlation between strength and functional variables. CONCLUSION: Handheld Dynamometer seems to be a reliable option to measure knee extension muscle strength, particularly when two measurements are performed and their average is reported.


Assuntos
Articulação do Joelho , Joelho , Estudos Transversais , Humanos , Joelho/fisiologia , Articulação do Joelho/fisiologia , Força Muscular/fisiologia , Dinamômetro de Força Muscular , Reprodutibilidade dos Testes
5.
JMIR Form Res ; 6(4): e32558, 2022 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-35412459

RESUMO

BACKGROUND: Despite the potential of digital mental health to provide cost-effective mental health care, its adoption in clinical settings is limited, and little is known about the perspectives and practices of mental health professionals regarding its implementation or the factors influencing these perspectives and practices. OBJECTIVE: This study aims to characterize in depth the perspectives and practices of mental health professionals regarding the implementation of digital mental health and explore the factors affecting such perspectives and practices. METHODS: A qualitative study using in-depth semistructured interviews with Portuguese mental health professionals (N=13)-psychologists and psychiatrists-was conducted. The transcribed interviews were thematically analyzed. RESULTS: Mental health professionals deemed important or engaged in the following practices during the implementation of digital mental health: indication evaluation, therapeutic contract negotiation, digital psychological assessment, technology setup and management, and intervention delivery and follow-up. Low-threshold accessibility and professionals' perceived duty to provide support to their clients facilitated the implementation of digital mental health. Conversely, the lack of structured intervention frameworks; the unavailability of usable, validated, and affordable technology; and the absence of structured training programs inhibited digital mental health implementation by mental health professionals. CONCLUSIONS: The publication of practice frameworks, development of evidence-based technology, and delivery of structured training seem key to expediting implementation and encouraging the sustained adoption of digital mental health by mental health professionals.

6.
Artigo em Inglês | MEDLINE | ID: mdl-35490091

RESUMO

OBJECTIVE: To describe the clinical experience with dalbavancin in the treatment of diabetic foot infection in a multidisciplinary unit of a second level hospital. METHODS: A retrospective, descriptive study was made with all patients with diabetic foot infection treated with dalbavancin in the Diabetic Foot Unit of Hospital Universitario Fundación Alcorcón, covering the period from September 2016 to December 2019. Demographic parameters and comorbidities, characteristics of the infection and treatment with dalbavancin were recorded. The cure rate is estimated at 90 days after finishing the treatment. RESULTS: A total of 23 patients with diabetic foot infection (osteomyelitis) started treatment with dalbavancin, 19 were men and the mean age was 65 years. The microorganisms most frequently isolated for the indication of treatment with dalbavancin were Staphylococcus aureus (11) and Corynebacterium striatum (7). Dalbavancin was used as a second choice therapy in 22 cases, in 11 due to toxicity from other antibiotics. The median duration of treatment was 5 (4-7) weeks; the most frequent dose of dalbavancin (8 patients) was 1000 mg followed by 500 mg weekly for 5 weeks. 3 patients presented mild side effects (nausea and gastrointestinal discomfort). At 90 days after completion of dalbavancin therapy, 87% (20) of the patients were cured (95% CI: 65.2%-94.52%). CONCLUSION: Patients with osteomyelitis due to gram-positive microorganisms who received as part of the multidisciplinary antibiotic treatment with dalbavancin, had a high rate of cure with adequate tolerance and few side effects. Dalbavancin offers a safe alternative in treating deep diabetic foot infection.


Assuntos
Doenças Transmissíveis , Diabetes Mellitus , Pé Diabético , Osteomielite , Idoso , Antibacterianos , Diabetes Mellitus/induzido quimicamente , Diabetes Mellitus/tratamento farmacológico , Pé Diabético/induzido quimicamente , Pé Diabético/complicações , Pé Diabético/tratamento farmacológico , Feminino , Humanos , Masculino , Osteomielite/tratamento farmacológico , Osteomielite/microbiologia , Estudos Retrospectivos , Teicoplanina/análogos & derivados
7.
Nat Cancer ; 3(4): 418-436, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35469014

RESUMO

Patient-derived organoids (PDOs) recapitulate tumor architecture, contain cancer stem cells and have predictive value supporting personalized medicine. Here we describe a large-scale functional screen of dual-targeting bispecific antibodies (bAbs) on a heterogeneous colorectal cancer PDO biobank and paired healthy colonic mucosa samples. More than 500 therapeutic bAbs generated against Wingless-related integration site (WNT) and receptor tyrosine kinase (RTK) targets were functionally evaluated by high-content imaging to capture the complexity of PDO responses. Our drug discovery strategy resulted in the generation of MCLA-158, a bAb that specifically triggers epidermal growth factor receptor degradation in leucine-rich repeat-containing G-protein-coupled receptor 5-positive (LGR5+) cancer stem cells but shows minimal toxicity toward healthy LGR5+ colon stem cells. MCLA-158 exhibits therapeutic properties such as growth inhibition of KRAS-mutant colorectal cancers, blockade of metastasis initiation and suppression of tumor outgrowth in preclinical models for several epithelial cancer types.


Assuntos
Anticorpos Biespecíficos , Neoplasias Epiteliais e Glandulares , Anticorpos Biespecíficos/farmacologia , Receptores ErbB/metabolismo , Humanos , Imidazóis , Neoplasias Epiteliais e Glandulares/metabolismo , Células-Tronco Neoplásicas/metabolismo , Organoides , Pirazinas , Receptores Acoplados a Proteínas G/metabolismo
8.
Ann Clin Biochem ; : 45632221090896, 2022 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-35352994
9.
Artigo em Inglês | MEDLINE | ID: mdl-35270518

RESUMO

Following the WHO's declaration of a public health emergency due to the COVID-19 outbreak, the subsequent quarantine and confinement measures that were adopted, including distance learning measures, were shown to have caused a significant deterioration in the mental health of medical students. The goal of this study was to explore the mediating role of resilience and life satisfaction in the relationship between perceived stress and burnout among medical students in the context of COVID-19. A transversal assessment was performed using an online questionnaire, to which 462 students responded. The instruments applied were the Perceived Stress Scale-10, the Resilience Scale-25 items, the Satisfaction with Life Scale (SWLS), and the Burnout Scale (Oldenburg Inventory). A regression model was estimated for each dimension of burnout. The results revealed that resilience and life satisfaction play a mediating role in the association between stress and the dimensions of burnout. This suggests that measures of promoting mental health based on resilience and improving perceptions of life should be implemented.


Assuntos
COVID-19 , Estudantes de Medicina , Esgotamento Psicológico , COVID-19/epidemiologia , Estudos Transversais , Humanos , Pandemias , Satisfação Pessoal , SARS-CoV-2 , Estudantes de Medicina/psicologia
11.
Sensors (Basel) ; 22(4)2022 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-35214383

RESUMO

There is much evidence pointing out eye movement alterations in several neurological diseases. To the best of our knowledge, this is the first video-oculography study describing potential alterations of eye movements in the post-COVID-19 condition. Visually guided saccades, memory-guided saccades, and antisaccades in horizontal axis were measured. In all visual tests, the stimulus was deployed with a gap condition. The duration of the test was between 5 and 7 min per participant. A group of n=9 patients with the post-COVID-19 condition was included in this study. Values were compared with a group (n=9) of healthy volunteers whom the SARS-CoV-2 virus had not infected. Features such as centripetal and centrifugal latencies, success rates in memory saccades, antisaccades, and blinks were computed. We found that patients with the post-COVID-19 condition had eye movement alterations mainly in centripetal latency in visually guided saccades, the success rate in memory-guided saccade test, latency in antisaccades, and its standard deviation, which suggests the involvement of frontoparietal networks. Further work is required to understand these eye movements' alterations and their functional consequences.


Assuntos
COVID-19 , Movimentos Oculares , Piscadela , Humanos , SARS-CoV-2 , Movimentos Sacádicos
12.
Nutrients ; 14(4)2022 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-35215379

RESUMO

The substitution of minimally processed food and culinary home preparations for ready-to-eat products is increasing worldwide, which is overlooked as a cause of concern. The technological developments and the rise in highly processed food availability have introduced the concept of ultra-processed food (UPF). Food classification systems based on processing are now a new basis for epidemiological research. Different results from these classifications might influence conclusions on the population's consumption of UPF or its association with health outcomes. The aim of this study was to compare classification systems and to find out if their results are comparable when evaluating the extent of high/UPF on the overall diet. Portuguese data from the year 2000 was extracted from the DAFNE-AnemosSoft, and 556 food/beverages items were classified according to five systems. The contribution of UPF was calculated as a percentage of total available amount and discrepancy ranges used for comparisons. Results of UPF availability contributions were: NOVA 10.2%; UNC 15.2%; IFPRI 16.7%; IFIC 17.7%; IARC 47.4%. The highest discrepancy ranges were from alcoholic beverages (97.4%), milk/milk products (94.2%), sugar/sugar products (90.1%), added lipids (74.9%), and cereals/cereal products (71.3%). Inconsistencies among classifications were huge and the contribution from highly/UPF presented high discrepancies. Caution must be taken when comparing and interpreting such data.


Assuntos
Fast Foods , Manipulação de Alimentos , Dieta , Inquéritos sobre Dietas
13.
Sensors (Basel) ; 22(3)2022 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-35161731

RESUMO

Recently, fall risk assessment has been a main focus in fall-related research. Wearable sensors have been used to increase the objectivity of this assessment, building on the traditional use of oversimplified questionnaires. However, it is necessary to define standard procedures that will us enable to acknowledge the multifactorial causes behind fall events while tackling the heterogeneity of the currently developed systems. Thus, it is necessary to identify the different specifications and demands of each fall risk assessment method. Hence, this manuscript provides a narrative review on the fall risk assessment methods performed in the scientific literature using wearable sensors. For each identified method, a comprehensive analysis has been carried out in order to find trends regarding the most used sensors and its characteristics, activities performed in the experimental protocol, and algorithms used to classify the fall risk. We also verified how studies performed the validation process of the developed fall risk assessment systems. The identification of trends for each fall risk assessment method would help researchers in the design of standard innovative solutions and enhance the reliability of this assessment towards a homogeneous benchmark solution.


Assuntos
Dispositivos Eletrônicos Vestíveis , Acidentes por Quedas/prevenção & controle , Algoritmos , Reprodutibilidade dos Testes , Medição de Risco
14.
JMIR Cancer ; 8(1): e33550, 2022 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-35166682

RESUMO

BACKGROUND: Despite the efficacy of psychosocial interventions in minimizing psychosocial morbidity in breast cancer survivors (BCSs), intervention delivery across survivorship is limited by physical, organizational, and attitudinal barriers, which contribute to a mental health care treatment gap in cancer settings. OBJECTIVE: The aim of this study is to develop iNNOV Breast Cancer (iNNOVBC), a guided, internet-delivered, individually tailored, acceptance and commitment therapy-influenced cognitive behavioral intervention program aiming to treat mild to moderate anxiety and depression in BCSs as well as to improve fatigue, insomnia, sexual dysfunction, and health-related quality of life in this group. This study also aims to evaluate the usefulness, usability, and preliminary feasibility of iNNOVBC. METHODS: iNNOVBC was developed using a user-centered design approach involving its primary and secondary end users, that is, BCSs (11/24, 46%) and mental health professionals (13/24, 54%). We used mixed methods, namely in-depth semistructured interviews, laboratory-based usability tests, short-term field trials, and surveys, to assess iNNOVBC's usefulness, usability, and preliminary feasibility among these target users. Descriptive statistics were used to characterize the study sample, evaluate performance data, and assess survey responses. Qualitative data were recorded, transcribed verbatim, and thematically analyzed. RESULTS: Overall, participants considered iNNOVBC highly useful, with most participants reporting on the pertinence of its scope, the digital format, the relevant content, and the appropriate features. However, various usability issues were identified, and participants suggested that the program should be refined by simplifying navigation paths, using a more dynamic color scheme, including more icons and images, displaying information in different formats and versions, and developing smartphone and tablet versions. In addition, participants suggested that tables should be converted into plain textboxes and data visualization dashboards should be included to facilitate the tracking of progress. The possibility of using iNNOVBC in a flexible manner, tailoring it according to BCSs' changing needs and along the cancer care continuum, was another suggestion that was identified. CONCLUSIONS: The study results suggest that iNNOVBC is considered useful by both BCSs and mental health professionals, configuring a promising point-of-need solution to bridge the psychological supportive care gap experienced by BCSs across the survivorship trajectory. We believe that our results may be applicable to other similar programs. However, to fulfill their full supportive role, such programs should be comprehensive, highly usable, and tailorable and must adopt a flexible yet integrated structure capable of evolving in accordance with survivors' changing needs and the cancer continuum.

15.
BMC Ophthalmol ; 22(1): 79, 2022 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-35168601

RESUMO

BACKGROUND: The purpose of this study is to describe measurements using a newly developed modified Goldmann convex tonometer (CT) 1 year after myopic laser refractive surgery. Intraocular pressure (IOP) measurements were compared with IOP values obtained by Goldmann applanation tonometer (GAT), and Ocular Response Analyzer (ORA). METHODS: Prospective double-masked study performed on thirty eyes of thirty patients that underwent laser in situ keratomileusis (LASIK; n = 19) or photorefractive keratectomy (PRK; n = 11). IOP was measured before and 3 and 12 months after surgery. Intraclass correlation coefficient (ICC) and Bland-Altman plot were calculated to assess the agreement between GAT, CT, IOPg (Goldmann-correlated IOP) and IOPcc (corneal-compensated IOP) from ORA. RESULTS: Twelve months after LASIK, IOP measured with CT showed the best correlation with IOP measured with GAT before surgery (GATpre) (ICC = 0.886, 95% CI: 0.703-0.956) (15.60 ± 3.27 vs 15.80 ± 3.22; p < 0.000). However, a moderate correlation was found for IOP measured with IOPcc and CT 12 months after LASIK (ICC = 0.568, 95% CI: - 0.185 - 0.843) (15.80 ± 3.22 vs 12.87 ± 2.77; p < 0.004). Twelve months after PRK, CT showed a weak correlation (ICC = - 0.266, 95% CI: - 3.896 - 0.663), compared to GATpre (17.30 ± 3.47 vs 16.01 ± 1.45; p < 0.642), as well as poor correlation (ICC = 0.256, 95% CI: - 0.332 - 0.719) with IOPcc (17.30 ± 3.47 vs 13.38 ± 1.65; p < 0.182). CONCLUSIONS: Twelve months after LASIK, IOP measured with CT strongly correlated with GAT before surgery and could therefore provide an alternative method for measuring IOP after this surgery. More studies regarding this new convex prism are needed to assess its accuracy.


Assuntos
Pressão Intraocular , Ceratomileuse Assistida por Excimer Laser In Situ , Córnea/cirurgia , Humanos , Lasers de Excimer/uso terapêutico , Polímeros , Estudos Prospectivos , Tonometria Ocular
16.
BMC Health Serv Res ; 22(1): 189, 2022 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-35151290

RESUMO

BACKGROUND: This article investigates the extent and sources of late diagnosis of cancer in Tanzania, demonstrating how delayed diagnosis was patterned by inequities rooted in patients' socio-economic background and by health system responses. It provides evidence to guide equity-focused policies to accelerate cancer diagnosis. METHODS: Tanzanian cancer patients (62) were interviewed in 2019. Using a structured questionnaire, respondents were encouraged to recount their pathways from first symptoms to diagnosis, treatment, and in some cases check-ups as survivors. Patients described their recalled sequence of events and actions, including dates, experiences and expenditures at each event. Socio-demographic data were also collected, alongside patients' perspectives on their experience. Analysis employed descriptive statistics and qualitative thematic analysis. RESULTS: Median delay, between first symptoms that were later identified as indicating cancer and a cancer diagnosis, was almost 1 year (358 days). Delays were strongly patterned by socio-economic disadvantage: those with low education, low income and non-professional occupations experienced longer delays before diagnosis. Health system experiences contributed to these socially inequitable delays. Many patients had moved around the health system extensively, mainly through self-referral as symptoms worsened. This "churning" required out-of-pocket payments that imposed a severely regressive burden on these largely low-income patients. Causes of delay identified in patients' narratives included slow recognition of symptoms by facilities, delays in diagnostic testing, delays while raising funds, and recourse to traditional healing often in response to health system barriers. Patients with higher incomes and holding health insurance that facilitated access to the private sector had moved more rapidly to diagnosis at lower out-of-pocket cost. CONCLUSIONS: Late diagnosis is a root cause, in Tanzania as in many low- and middle-income countries, of cancer treatment starting at advanced stages, undermining treatment efficacy and survival rates. While Tanzania's policy of free public sector cancer treatment has made it accessible to patients on low incomes and without insurance, reaching a diagnosis is shown to have been for these respondents slower and more expensive the greater their socio-economic disadvantage. Policy implications are drawn for moving towards greater social justice in access to cancer care.


Assuntos
Gastos em Saúde , Neoplasias , Humanos , Renda , Neoplasias/diagnóstico , Neoplasias/terapia , Pobreza , Fatores Socioeconômicos , Tanzânia/epidemiologia
17.
Br J Cancer ; 126(3): 331-350, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34811504

RESUMO

Prostate cancer is a global cancer burden and considerable effort has been made through the years to identify biomarkers for the disease. Approximately a decade ago, the potential of analysing extracellular vesicles in liquid biopsies started to be envisaged. This was the beginning of a new exciting area of research investigating the rich molecular treasure found in extracellular vesicles to identify biomarkers for a variety of diseases. Vesicles released from prostate cancer cells and cells of the tumour microenvironment carry molecular information about the disease that can be analysed in several biological fluids. Numerous studies document the interest of researchers in this field of research. However, methodological issues such as the isolation of vesicles have been challenging. Remarkably, novel technologies, including those based on nanotechnology, show promise for the further development and clinical use of extracellular vesicles as liquid biomarkers. Development of biomarkers is a long and complicated process, and there are still not many biomarkers based on extracellular vesicles in clinical use. However, the knowledge acquired during the last decade constitutes a solid basis for the future development of liquid biopsy tests for prostate cancer. These are urgently needed to bring prostate cancer treatment to the next level in precision medicine.


Assuntos
Biomarcadores Tumorais/análise , Ácidos Nucleicos Livres/análise , Detecção Precoce de Câncer/métodos , Vesículas Extracelulares/metabolismo , Biópsia Líquida/métodos , Células Neoplásicas Circulantes/patologia , Neoplasias da Próstata/diagnóstico , Animais , Ácidos Nucleicos Livres/genética , Ácidos Nucleicos Livres/metabolismo , Vesículas Extracelulares/genética , Humanos , Masculino , Medicina de Precisão , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo
18.
Circ Econ Sustain ; 1(4): 1439-1461, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34888570

RESUMO

In this article, we present breakthroughs and challenges in vaccine development for COVID-19 pandemic, discussing issues related to pandemic preparedness and their implications for circular bioeconomy and sustainability. Notwithstanding the unprecedented accelerated speed of COVID-19 vaccine development, just 9 months after the emergence of the pandemic in Wuhan, China, benefiting from previous developments in SARS and MERS vaccines, significant gaps persist in global vaccine preparedness. These gaps include issues related to immunity and protection, particularly to the limited vaccine protection against recent emergence of concerning new viral variants in the UK, South Africa, and Brazil and the consequent need for vaccine redesign. We examine these gaps and discuss the main issues that could impact on global vaccine availability in the current pandemic scenario: (1) breakthroughs and constraints in development and production of leading global COVID-19 vaccines; (2) innovation and technological development advances and gaps, providing information on global patent assignees for COVID-19, SARS, and MERS vaccine patents; (3) local capacity for development and production of COVID-19, SARS, and MERS vaccines in three emerging agro-based countries (India, Brazil, and South Africa); and (4) future scenarios, examining how these issues and vaccines redesign for new SARS-CoV-2 variants could impact on global access to vaccines and implications for circular bioeconomy and sustainability in the post-COVID era.

19.
Sensors (Basel) ; 21(23)2021 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-34884093

RESUMO

The purpose of this study was to investigate if the use of an ankle foot orthosis in passive mode (without actuation) could modify minimum foot clearance, and if there are any compensatory mechanisms to enable these changes during treadmill gait at a constant speed. Eight participants walked on an instrumented treadmill without and with an ankle foot orthosis on the dominant limb at speeds of 0.8, 1.2, and 1.6 km/h. For each gait cycle, the minimum foot clearance and some gait linear kinematic parameters were calculated by an inertial motion capture system. Additionally, maximum hip and knee flexion and maximum ankle plantar flexion were calculated. There were no significant differences in the minimum foot clearance between gait conditions and lower limbs. However, differences were found in the swing, stance and step times between gait conditions, as well as between limbs during gait with orthosis (p < 0.05). An increase in hip flexion during gait with orthosis was observed for all speeds, and different ankle ranges of motion were observed according to speed (p < 0.05). Thus, the use of an ankle foot orthosis in passive mode does not significantly hinder minimum foot clearance, but can change gait linear and angular parameters in non-pathological individuals.


Assuntos
Tornozelo , Órtoses do Pé , Articulação do Tornozelo , Fenômenos Biomecânicos , , Marcha , Humanos , Amplitude de Movimento Articular , Caminhada
20.
BMJ Open ; 11(12): e047623, 2021 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-34872992

RESUMO

OBJECTIVES: High-quality data are crucial for guiding decision-making and practising evidence-based healthcare, especially if previous knowledge is lacking. Nevertheless, data quality frailties have been exposed worldwide during the current COVID-19 pandemic. Focusing on a major Portuguese epidemiological surveillance dataset, our study aims to assess COVID-19 data quality issues and suggest possible solutions. SETTINGS: On 27 April 2020, the Portuguese Directorate-General of Health (DGS) made available a dataset (DGSApril) for researchers, upon request. On 4 August, an updated dataset (DGSAugust) was also obtained. PARTICIPANTS: All COVID-19-confirmed cases notified through the medical component of National System for Epidemiological Surveillance until end of June. PRIMARY AND SECONDARY OUTCOME MEASURES: Data completeness and consistency. RESULTS: DGSAugust has not followed the data format and variables as DGSApril and a significant number of missing data and inconsistencies were found (eg, 4075 cases from the DGSApril were apparently not included in DGSAugust). Several variables also showed a low degree of completeness and/or changed their values from one dataset to another (eg, the variable 'underlying conditions' had more than half of cases showing different information between datasets). There were also significant inconsistencies between the number of cases and deaths due to COVID-19 shown in DGSAugust and by the DGS reports publicly provided daily. CONCLUSIONS: Important quality issues of the Portuguese COVID-19 surveillance datasets were described. These issues can limit surveillance data usability to inform good decisions and perform useful research. Major improvements in surveillance datasets are therefore urgently needed-for example, simplification of data entry processes, constant monitoring of data, and increased training and awareness of healthcare providers-as low data quality may lead to a deficient pandemic control.


Assuntos
COVID-19 , Confiabilidade dos Dados , Humanos , Pandemias , Pesquisa , SARS-CoV-2
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